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Showing 7 results for Apoptosis
In vitro cytotoxicity and apoptotic inducing activity of the synthesized 4-aryl-4H-chromenes derivatives against human cancer cell lines
Majid Mahmoodi , Saeid Rajabalian , A Foroumadi , Saeid Hidarykeshel , Malihe Sadat Safavi , A Khoshzaban , Korous Divsalar , Mohammad Ali Mohagheghi ,
Volume 67, Issue 6 (9-2009)
Abstract
Background: 4-Aryl-4H-chromenes are novel anticancer agents which induce apoptosis in cancer cells. These compounds were found to induce apoptosis by targeting the tubulin/microtubule system in cell proliferation process. The aim of this study was to report cyototoxic and apoptosis inducing activities of a new series of synthesized 4-aryl-4H-chromenes compounds. Methods: The in vitro cytotoxic activity of the synthesized 4-aryl-4H-chromenes was investigated against a paned of human cancer cell lines including MCF-7 (breast carcinoma), A549 (lung carcinoma), HEPG-2 (liver carcinoma), SW-480 (colon adenocarcinoma), U87-MG (glioblastoma), 1321N1 (astrocytoma), and DAOY (medulloblastoma). The percentage of growth inhibitory activity was evaluated using MTT colorimetric assay versus controls not treated with test derivatives. The data for etoposide, a well known anticancer drug, was included for comparison. For each compound, the 50% inhibitory concentration (IC50) were determined. Apoptosis inducing activity were assessed by DAPI staining. Results: Preliminary screening showed that those chromenes analogs bearing phenyl-isoxazole-3-yl substitution or the derivatives containing methoxyphenyl in chromene ring exhibited cytotoxic and apoptotic inducing activity comparable with or even superior than the reference drug, etoposide. The compounds without this type of substitution have lower activity. Conclusions: Replacement of 3, 4, 5-trimethoxyphenyl group with thiazol ring in the synthesized derivatives reduced the cytotoxic activity. However, the derivatives with phenyl-isoxazole analogue showed potent cytotoxic and apoptotic inducing activity.
Evaluation of chemical composition, antioxidant, antibacterial, cytotoxic and apoptotic effects of Aloysia citrodora extract on colon cancer cell line
Amir Mirzaie , Seyed Ataollah Sadat Shandiz, Hassan Noorbazargan , Elahe Ali Asgary,
Volume 74, Issue 3 (6-2016)
Abstract

Background: Aloysia citrodora belongs to the Verbenaceae family of plants, a well-known herbal medicine in Iran. The aim of the present study was to investigate the chemical composition, antioxidant, antibacterial, cytotoxic and apoptotic effect of A. citrodora extract against human colon cancer (HT29) cells by using real-time polymerase chain reaction and flow-cytometry methods.

Methods: This experimental study was carried out in Islamic Azad University, East Tehran Branch, from March to September of 2014. At first, the A. citrodora chemical constituents were analyzed by gas chromatography-mass spectrometry (GC-MS) technique. In addition, antioxidant assay, antibacterial and anti-cancer effect was performed using 1,1-diphenyl-2-picrylhydrazyl (DPPH), disk diffusion and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) methods, respectively. The half maximal inhibitory concentration (IC50) value was calculated. We extracted total RNA molecules by using RNX solution, after which cDNA was synthesized. Finally, the pro-apoptotic (Bax) and anti-apoptotic (Bcl2) gene expression was performed by real-time polymerase chain reaction and apoptotic effects were analyzed using Flow-cytometry method.

Results: GC-MS analysis of Aloysia citrodora extract was shown 37 major components and the most frequent component was belonged to Spathulenol (17.57%) and Caryophyllene oxide (15.15%) The antioxidant activity of the extract was IC50= 0.6±0.03 mg/ml. The maximum and minimum antibacterial effects of extract were belonged to gram-negative and gram-positive bacteria, respectively. Cytotoxic results revealed that the A.citrodora extract have IC50= 20.1±0.78 mg/ml against colon cancer (HT29) cell line and real-time polymerase chain reaction results showed the expression level of Bax and Bcl2 was increased and decreased respectively in colon cancer cell line (3.470±0.72 (P< 0.05), 0.43±0.35 (P< 0.05)). In addition, the flow-cytometry results indicated the 38.66% apoptosis in colon cancer cell line.

Conclusion: According to the results, it seems that A. citrodora extract has potential antioxidant, antibacterial and anticancer effects and it suggested that further studies were performed for A. citrodora pharmaceutical importance.


Study of chemical composition and characteristics of Centurea cyanus extract on colon cancer cell line and analysis of apoptosis gene expression
Amir Mirzaie , Shoreh Zare Karizi ,
Volume 74, Issue 9 (12-2016)
Abstract

Background: Centaurea cyanus is an endemic and well-known herbal medicine in Iran, is an annual flowering plant in the family of Asteraceae. The flowers are the part used in modern herbal medicine and are considered to have tonic, stimulant and emmenagogue properties, with action similar to that of blessed thistle. The aim this study was to investigate the phytochemical constituents of C. cyanus extract, its antioxidant, anti-tumor and anti-bacterial activities.

Methods: This experimental study was conducted from June to January of 2015 in Islamic Azad University of Varamin, Iran. At first, the phytochemical components of C. cyanus extract was analyzed using gas chromatography–mass spectrometry (GC-MS) method. Subsequently, the antibacterial potential of the extract was evaluated against 4 pathogenic bacteria including Staphylococcus aureus, Streptococcus pyogenes, Psedomonas aeroginosa and Klebsiella pnemoniae via minimum inhibitory concentration (MIC) mathod. Moreover, the anti-oxidant and anti-tumor activities of extract on colon cancer cell line (HT29) were investigate using DPPH and MTT colorimetric methods, respectively. Finally, the Bax and Bcl2 apoptosis gene expression level was analyzed by quantitative Real-time PCR technique.

Results: GC-MS analysis of C. cyanus extract was shown 19 major components and the most frequent component was belonged to n-Hexadecanoic acid (36.4%) and Linoleic acid (19.3%). The maximum antibacterial activity of extract was observed on S. aureus and P. aeroginosa isolates. The antioxidant activity of the extract was 0.109±0.07 mg/ml. Moreover, the MTT results show that extract had IC50= 26.04±0.45 on HT29 cell line. The Real-time PCR results showed the expression level of Bax and Bcl2 was significantly increased and decreased respectively in colon cancer cell line (2.63±0.54 (P< 0.05), 0.38±0.72 (P< 0.05)).

Conclusion: The results of this study show that the extract had significant anti-bacterial and anti-cancer effects and it appear that the extract has potential uses for pharmaceutical industries.


A quantitative investigation of the Bid gene expression in biopsies from colorectal adenomas
Fateme Sadat Kia , Ehsan Nazemalhosseini-Mojarad, Flora Forouzesh,
Volume 76, Issue 2 (5-2018)
Abstract
Background: Most of colorectal cancers arise from intestinal polyps. Evaluating of the expression level of genes that are involved in tumors growth and development, may consider as diagnostic factor of malignancy in the polyps. Failure of apoptosis is one of the causes of cancers. One of the key molecules in this pathway is Bid gene which connects the extrinsic to the intrinsic apoptosis pathways. The aim of this study was to investigate the quantitative expression of Bid gene in colorectal adenomatous polyps compared to control group.
Methods: The investigated population was chosen from the cases with colonic polyps that referred to the Taleghani Hospital, Tehran, Iran, from April 2014 to May 2016. 22 biopsy samples from patients with adenomatous polyps and 10 samples from healthy individuals as control group were selected. Demographic and clinical properties were collected from patients' files. The Bid gene expression was evaluated using Real-time PCR by ABI 7500 (Applied Biosystems Inc., Foster City, CA, USA). Results were analyzed by the ABI 7500 system SDS version 2.3 and GraphPad Prism, version 5 (GraphPad Software Inc., La Jolla, CA, USA). the expression changes of the intended gene in target groups were compared with the normal tissues using the 2-∆∆CT equation.
Results: Based on the quantitative real-time PCR, the gene expression of Bid gene significantly increased in adenomatous polyps in comparison with the control group (healthy individuals) (RQ>2). Also, polyps were seen in ascending colon, transverse colon, descending colon and rectum showed increased expression compared to control group, but in the sigmoid section of the intestine, there was no change in expression of Bid gene compared to control group.
Conclusion: According to the present study, the expression of Bid gene increased in adenomatous polyps, compared with the normal tissue (healthy group). It suggests that Bid gene by increasing the expression in response to the onset of dysplasia and disruption of the apoptotic cycle, it tries to compensate for the apoptosis.

Anti-proliferative and pro-apoptotic effects of gallic acid on the breast adenocarcinoma cell lines SKBR3 versus normal fibroblast cells (HU-02)
Roghayeh Larki, Leila Rouhi , Seyed Hossein Hejazi ,
Volume 76, Issue 3 (6-2018)
Abstract
Background: Breast cancer is a malignant proliferation of epithelial cells that lining the ducts or lobules of the breast. Breast cancer is the second common cancer (after lung cancer) in women. Gallic acid, being a polyphenols, has been reported for its antiproliferative activity against many cancer cell lines. Objective of the present study is effect of gallic acid on proliferation and apoptosis of the human breast adenocarcinoma cell lines SKBR3 and normal fibroblasts cells.
Methods: This experimental study was performed in cellular and developmental biology of Shahrekord Islamic Azad University, Iran from April to August 2015. For anti-cancer activity, in this study SKBR3 cells and normal fibroblast cells (HU-02) were cultured in Dulbecco's modified eagle's medium, DMEM (Gibco, Life Technologies, Inc., New York, USA) medium with 10% fetal bovine serum, FBS (Gibco, Life Technologies, Inc., New York, USA). The SKBR3 and normal fibroblast cells were treated in the medium of DMEM medium and gallic acid (20, 40, 80, 100 and 200 µg/ml) for 24, 48 and 72 hours. Cells viability was assessed by MTS (Methyl- Thiazol-) assay. Cells were seeded at 5×103 cells/ml in 96 well plates and incubated for 24 hours. Then metabolites of bacteria were added, after indicated times MTS (20µl) was added and the absorbance was measured at 492 nm using ELISA plate reader. The percentage of apoptosis induction was determined by flow cytometry analysis using Annexin-V fluorescein isothiocyanate (FITC) kit (BioVision Products, CA, USA) in 20, 40, 80, 100 and 200 µg/ml concentration of gallic acid at 48 hours incubation.
Results: Gallic acid decreases significantly the viability of SKBR3 cell line in a time and dose dependent manner. So that the most effective concentration of this substance was 200 µg/ml and 72 hours after treatment (P< 0.05). According to the data of Annexin-PI, the highest apoptosis induction rate was seen in 200 µg/ml (P< 0.05). While gallic acid in various concentrations had no significant effect on normal fibroblast cells.
Conclusion: Objective of the present study is effect of gallic acid on proliferation and apoptosis of the human breast adenocarcinoma cell lines SKBR3 and normal fibroblasts cells.

Effects of Iron oxide functionalized by Glutamic acid and 2-pyridinecarboxaldehyde thiosemicarbazone against lung cancer A549 cells and analysis of NDRG1 gene expression
Alireza Habibi, Seyed Ataollah Sadat Shandiz , Ali Salehzadeh, Zeinab Moradi-Shoeili,
Volume 78, Issue 7 (10-2020)
Abstract
Background: Lung cancer is a disease with high mortality rate that conventional drug treatments have not been successful in controlling it. The activity of iron chelators in various studies has been considered by scientists as a new treatment strategy. The primary objective of this study was to synthesize a novel Fe3O4 thiosemicarbazone complex and investigate its anti-proliferative activity against A549 cells of lung cancer.
Methods: This experimental study was carried out in Islamic Azad University of Rasht Branch, from September of 2018 to September 2019. First thiosemicarbazone (PTSC) was synthesized by the method of the condensation reaction of amine and aldehyde groups. Also, the Fe3O4 nanoparticulates were synthesized using the co-precipitation method in the presence of glutamic acid. Then, Fe3O4@Glu complex functionalized with bio-reactive PTSC moiety. Besides, morphological characteristics of Fe3O4@Glu/PTSC complex were determined by scanning electron microscope (SEM) images. The cell viability was detected in 62.5, 125, 250, 500, and 1000 µg/ml for treated cells with Fe3O4@Glu/PTSC complex via MTT assay. Changes of NDRG1 gene expression the level in treated cells were investigated via qRT-PCR analysis. Therefore, total RNA was extracted after culturing the cells and cDNA of NDRG1 and GAPDH genes as the study and control gene was obtained, respectively. Ultimately, the level of NDRG1 gene expression was compared with level of GAPDH mRNA expression via the 2– ΔΔCt method.
Results: SEM images confirmed the sphericality of the Fe3O4 @ Glu / PTSC complex. The size of the nanoparticles was uniform and about 52-23 nm. The cell survival assay (MTT) results revealed the anti-proliferative properties of this complex in a dose-dependent manner (IC50=135.6 µM/ml). In treated cells, the gene expression of NDRG1 was 1.8-fold higher after 12 h. However, after 24 hours of incubation, this gene was showed a 0.67-fold decrease in expression compared to the control group.
Conclusion: The results of the present study suggest that Fe3O4@Glu/PTSC nanoparticulates by a decrease of NDRG1 expression, exhibit effective anti-cancer activity against lung cancer cells.

The effect of flavonoids in the treatment of Alzheimer’s disease: review article
Adele Jafari, Behrooz Khakpour Taleghani ,
Volume 79, Issue 1 (4-2021)
Abstract
Alzheimer’s disease (AD) is the most prevalent age-related neurodegenerative disorder worldwide, and no cure or prevention has been found for it. Extracellular senile plaque and intracellular neurofibrillary tangles are two important histopathological hallmarks of AD, which are both harmful for the cell. Senile plaques are composed of amyloid beta and neurofibrillary tangles are formed by hyperphosphorylated Tau proteins. In AD, several cellular changes also occur, including oxidative stress, neuroinflammation, accumulation of misfolded proteins, and mitochondrial dysfunction. These events promote neuronal death and finally decline memory and cognition. Lack of success of the available chemical anti-AD therapeutic agents has attracted attention to the concept of the administration of naturally occurring compounds in the treatment of AD. These compounds can be employed as a substitute for the chemical agents or complementary regimens. Several natural products are deemed capable of crossing the blood-brain barrier and are known for their central nervous system-related activity. Among the most important of them are flavonoids. Recent evidence has demonstrated their neuroprotective effects. These plant-derived compounds have strong effects on dementia-induced brain disorders because of their ability to produce antioxidants. Numerous mechanisms have been proposed for flavonoids through which they act for the prevention or recession of the disease process. According to evidence, flavonoids inhibit acetylcholinesterase (AChE), β-secretase (BACE1) and free radicals. They reduce the amyloid-beta toxicity and prevent the formation of neurofibrillary tangles. Also, they help to inhibit apoptosis induced by oxidative stress and neuroinflammation. These products have a role in synaptic plasticity and the generation of new neurons. They can affect various signaling pathways like Extracellular signal-regulated kinase (Erk), Phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK). Overall, these processes can prevent the progression of AD and improve cognitive symptoms. In the present paper, the effect of the most important plant-derived flavonoids is briefly reviewed in different models of AD. The mechanism of action and the important signaling pathways in reducing neuroinflammation, apoptosis, and oxidative damage are discussed. It is concluded that despite the beneficial effect of these compounds, future studies are needed before flavonoids can be used as a drug in the treatment of Alzheimer’s disease.
 

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